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Int. J. Mol. Sci. 2018, 19(1), 47; https://doi.org/10.3390/ijms19010047

Characterizing Metastatic HER2-Positive Gastric Cancer at the CDH1 Haplotype

1
Immunopathology and Cancer Biomarkers, IRCCS CRO National Cancer Institute, 33081 Aviano, Italy
2
Medical Oncology, IRCCS, CRO National Cancer Institute, 33081 Aviano, Italy
3
Department of Medicine, School of Medical Oncology, University of Udine, 0432 Udine, Italy
4
SSD Oncology, Ospedale Civile Alghero, 07041 Alghero, Italy
5
Operative Unit of Pathology Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, 07100 Sassari, Italy
6
Institute of Biomolecular Chemistry, Cancer Genetics Unit, C.N.R., 07100 Sassari, Italy
7
Gastroenterology, IRCCS CRO National Cancer Institute, 33081 Aviano, Italy
8
Pathology, IRCCS CRO National Cancer Institute, 33081 Aviano, Italy
9
Medical Oncology Department, Santa Maria degli Angeli Hospital, 33170 Pordenone, Italy
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 28 November 2017 / Revised: 19 December 2017 / Accepted: 21 December 2017 / Published: 23 December 2017
(This article belongs to the Special Issue Molecular Features Distinguishing Gastric Cancer Subtypes)
View Full-Text   |   Download PDF [1226 KB, uploaded 24 December 2017]   |  

Abstract

The CDH1 gene, coding for the E-cadherin protein, is linked to gastric cancer (GC) susceptibility and tumor invasion. The human epidermal growth factor receptor 2 (HER2) is amplified and overexpressed in a portion of GC. HER2 is an established therapeutic target in metastatic GC (mGC). Trastuzumab, in combination with various chemotherapeutic agents, is a standard treatment for these tumors leading to outcome improvement. Unfortunately, the survival benefit is limited to a fraction of patients. The aim of this study was to improve knowledge of the HER2 and the E-cadherin alterations in the context of GC to characterize subtypes of patients that could better benefit from targeted therapy. An association between the P7-CDH1 haplotype, including two polymorphisms (rs16260A-rs1801552T) and a subset of HER2-positive mGC with better prognosis was observed. Results indicated the potential evaluation of CDH1 haplotypes in mGC to stratify patients that will benefit from trastuzumab-based treatments. Moreover, data may have implications to understanding the HER2 and the E-cadherin interactions in vivo and in response to treatments. View Full-Text
Keywords: E-cadherin; CDH1; HER2; metastatic gastric cancer; rs16260; rs1801552 E-cadherin; CDH1; HER2; metastatic gastric cancer; rs16260; rs1801552
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Caggiari, L.; Miolo, G.; Buonadonna, A.; Basile, D.; Santeufemia, D.A.; Cossu, A.; Palmieri, G.; De Zorzi, M.; Fornasarig, M.; Alessandrini, L.; Canzonieri, V.; Lo Re, G.; Puglisi, F.; Steffan, A.; Cannizzaro, R.; De Re, V. Characterizing Metastatic HER2-Positive Gastric Cancer at the CDH1 Haplotype. Int. J. Mol. Sci. 2018, 19, 47.

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